Autoacetylation-mediated phase separation of TIP60 is critical for its functions

Abstract

TIP60 is an important lysine acetyl transferase protein that participates in various essential cellular activities by catalyzing the post-translational acetylation of lysine residues on histones and various non-histone protein substrates. TIP60 typically localizes to the nucleus in a punctate foci pattern, although defining factors and mechanisms regulating the assembly of TIP60 foci and their spatial distribution inside the nucleus are not understood. In the present study, we report that TIP60 can undergo phase separation to form liquid like droplets in the nuclear compartment, which is facilitated by the presence of an intrinsically disordered region (IDR) located between its chromodomain and catalytic domain. Importantly, we identified that autoacetylation on lysine 187, located within the IDR region of TIP60, is important for nuclear localization, oligomer formation and phase separation. Finally, we observed that the phase separation of TIP60 promotes its interaction with its partner proteins and actively contribute to its cellular functions.